The sequelae of biochemical, cellular, and/or molecular events leading to the development of age-related macular degeneration (AMD), the leading cause of irreversible blindness in this country, are poorly understood.
Aims outlined in this proposal are directed toward continued morphological and molecular characterization of drusen, BLD, and Bruch's membrane, based on the general operating hypothesis that knowledge pertaining to the composition of these structures will provide insight into the pathobiology of AMD.
Other aims will test the hypothesis that RPE """"""""injury"""""""" and immune-mediated processes are intimately involved in early drusen biogenesis and, by extension, in the development of AMD. The specific identity of previously undescribed drusen-associated choriodal monocytes will be established. Additional aims will address a hypothesis predicting that the macula is more susceptible to degeneration in AMD because the structure and composition of Bruch's membrane in this region is different than that of extramacular regions. We anticipate that these foundational studies will continue to provide new knowledge about the pathobiology of drusen, BLD, Bruch's membrane, and the RPE that will contribute to a conceptual framework for pursuing additional basic and clinical research into the causes and prevention of AMD.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-VISB (01))
Program Officer
Dudley, Peter A
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University of Iowa
Schools of Medicine
Iowa City
United States
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Len, Alice C L; Powner, Michael B; Zhu, Ling et al. (2012) Pilot application of iTRAQ to the retinal disease Macular Telangiectasia. J Proteome Res 11:537-53
Helminen, M; Seitsonen, S; Jarva, H et al. (2012) A novel mutation W388X underlying properdin deficiency in a Finnish family. Scand J Immunol 75:445-8
Powner, Michael B; Scott, Andrew; Zhu, Meidong et al. (2011) Basement membrane changes in capillaries of the ageing human retina. Br J Ophthalmol 95:1316-22
Baehr, Wolfgang; Wensel, Ted; Hageman, Greg et al. (2011) Retinal ganglion cells: development, function, and disease. Vision Res 51:223
Gupta, Priya; Yee, Kenneth M P; Garcia, Patricia et al. (2011) Vitreoschisis in macular diseases. Br J Ophthalmol 95:376-80
Tulamo, Riikka; Frosen, Juhana; Junnikkala, Sami et al. (2010) Complement system becomes activated by the classical pathway in intracranial aneurysm walls. Lab Invest 90:168-79
Seitsonen, Sanna; Onkamo, Paivi; Torniainen, Suvi et al. (2010) Screening of DNA-variants in the properdin gene (CFP) in age-related macular degeneration (AMD). Mol Immunol 47:1334-6
Ryhänen, Tuomas; Hyttinen, Juha M T; Kopitz, Jürgen et al. (2009) Crosstalk between Hsp70 molecular chaperone, lysosomes and proteasomes in autophagy-mediated proteolysis in human retinal pigment epithelial cells. J Cell Mol Med 13:3616-31
Seitsonen, Sanna P; Onkamo, Paivi; Peng, Gang et al. (2008) Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration. PLoS One 3:e3833
Deban, Livija; Jarva, Hanna; Lehtinen, Markus J et al. (2008) Binding of the long pentraxin PTX3 to factor H: interacting domains and function in the regulation of complement activation. J Immunol 181:8433-40

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